Chronic obstructive pulmonary disease (COPD) includes conditions such as, e.g., chronic bronchitis and emphysema. COPD currently affects over 15 million people in the United States alone and is currently the third leading cause of death in the country. The primary cause of COPD is the inhalation of cigarette smoke, responsible for over 90% of COPD cases. The economic and social burden of the disease is substantial and is increasing.
Chronic bronchitis is characterized by chronic cough with sputum production. Due to airway inflammation, mucus hypersecretion, airway hyperresponsiveness, and eventual fibrosis of the airway walls, significant airflow and gas exchange limitations result.
Emphysema is characterized by the destruction of the lung parenchyma. This destruction of the lung parenchyma leads to a loss of elastic recoil and tethering which maintains airway patency. Because bronchioles are not supported by cartilage like the larger airways, they have little intrinsic support and therefore are susceptible to collapse when destruction of tethering occurs, particularly during exhalation.
Acute exacerbations of COPD (AECOPD) often require emergency care and inpatient hospital care. An AECOPD is defined by a sudden worsening of symptoms (e.g., increase in or onset of cough, wheeze, and sputum changes) that typically last for several days, but can persist for weeks. An AECOPD is typically triggered by a bacterial infection, viral infection, or pollutants, which manifest quickly into airway inflammation, mucus hypersecretion, and bronchoconstriction, causing significant airway restriction.
Despite relatively efficacious drugs (long-acting muscarinic antagonists, long-acting beta agonists, corticosteroids, and antibiotics) that treat COPD symptoms, a particular segment of patients known as “frequent exacerbators” often visit the emergency room and hospital with exacerbations and also have a more rapid decline in lung function, poorer quality of life, and a greater mortality risk.
Reversible obstructive pulmonary disease includes asthma and reversible aspects of COPD. Asthma is a disease in which bronchoconstriction, excessive mucus production, and inflammation and swelling of airways occur, causing widespread but variable airflow obstruction thereby making it difficult for the asthma sufferer to breathe. Asthma is further characterized by acute episodes of airway narrowing via contraction of hyper-responsive airway smooth muscle.
The reversible aspects of COPD include excessive mucus production and partial airway occlusion, airway narrowing secondary to smooth muscle contraction, and bronchial wall edema and inflation of the airways. Usually, there is a general increase in bulk (hypertrophy) of the large bronchi and chronic inflammatory changes in the small airways. Excessive amounts of mucus are found in the airways, and semisolid plugs of mucus may occlude some small bronchi. Also, the small airways are narrowed and show inflammatory changes.
In asthma, chronic inflammatory processes in the airway play a central role in increasing the resistance to airflow within the lungs. Many cells and cellular elements are involved in the inflammatory process including, but not limited to, mast cells, eosinophils, T lymphocytes, neutrophils, epithelial cells, and even airway smooth muscle itself. The reactions of these cells result in an associated increase in sensitivity and hyperresponsiveness of the airway smooth muscle cells lining the airways to particular stimuli.
The chronic nature of asthma can also lead to remodeling of the airway wall (i.e., structural changes such as airway wall thickening or chronic edema) that can further affect the function of the airway wall and influence airway hyper-responsiveness. Epithelial denudation exposes the underlying tissue to substances that would not normally otherwise contact the underlying tissue, further reinforcing the cycle of cellular damage and inflammatory response.
In susceptible individuals, asthma symptoms include recurrent episodes of shortness of breath (dyspnea), wheezing, chest tightness, and cough. Currently, asthma is managed by a combination of stimulus avoidance and pharmacology.
In severe cases of COPD and in AECOPD, patients also can experience a build-up of carbon dioxide (CO2), known as hypercapnia, which can create dangerous conditions such as acidosis (low pH of the blood). In respiratory-compromised lungs, blood returning to the heart may not have sufficient oxygen (O2) content, and may have too much CO2. These O2 and CO2 levels may affect the functioning of the patient, particularly during physical exertion. Low pH levels in the blood have been shown to correlate to the need for hospital readmission and higher mortality rates. O2 is often administered to COPD patients with severe symptoms to treat hypoxemia. However, evidence suggests administration of O2 can lead to high levels of CO2 in the blood. End stage (GOLD IV) COPD patients have no other options except lung transplant. However, such patients are generally poor candidates for transplant procedures due to co-morbid conditions. Perfluorocarbons (PFCs) have been used experimentally for liquid ventilation (e.g., liquid PFC has been used to fill the lung instead of air, vapour, or mist) in patients with lung injury and/or acute respiratory distress, and neonates. Some studies show PFC use to be safe, but no substantial benefit has been observed when used in this way.
Extracorporeal Membrane Oxygenators (ECMOs) have been used for removing CO2 in hypercapnic patients. Some are positioned outside the body and are supplied with blood from intra-venous and intra-arterial catheters. Other experimental attempts have placed a large gas exchange unit in the vena-cava. The gas exchange unit can be supplied with external air. However, this design has not been efficient enough to date for practical use.
Thus, a need exists for patients suffering from diseases of the lung. More specifically, a need exists for improved treatments for patients with hypercapnia to remove CO2 from the blood.